POS1319 OUTCOMES IN SYSTEMIC SCLEROSIS PATIENTS TREATED WITH RITUXIMAB AND MYCOPHENOLATE MOFETIL COMBINATION THERAPY COMPARED TO HEMATOLOGICAL STEM CELL TRANSPLANTATION
Authors: S. Keret, L. Kaly, A. Shouval, T. Zuckerman, I. Henig, A. Awisat, I. Rosner, N. Boulman, M. Rozenbaum, A. Dortort Lazar, G. Slobodin, D. Rimar
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Autologous hematological stem cell transplantation (AHSCT) is a grade A therapy for early diffuse progressive systemic sclerosis (SSc), that has been validated in three randomized controlled trials (RCT) compared to cyclophosphamide (CYC) [<b>1</b>]. CYC, however, is no longer considered the gold standard therapy for SSc and does not provide long-term benefit [<b>2</b>]. The efficacy of rituximab on skin and lung involvement in SSc has recently been demonstrated in an RCT, the DESIRES study. The combination of rituximab with mycophenolate mofetil (MMF) is a potential potent regimen for progressive SSc, that has not been evaluated compared to AHSCT. <h3>Objectives</h3> To retrospectively compare the outcomes of SSc patients in our cohort, fulfilling eligibility criteria for AHSCT studies, who received a combination therapy of MMF and rituximab, with patients who underwent AHSCT. <h3>Methods</h3> Repeated longitudinal assessments at baseline and every 6 months for 24 months, including modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) values, were compared between groups using a linear mixed model regression. Clinical improvement (CI) was defined as a decrease in mRSS by more than 25% or an increase in FVC by more than 10%. Event-free survival (EFS) was defined as the occurrence of death or the development of persistent major organ failure (heart, lung, kidney). Hazard ratios (HRs) and 95% CIs were calculated by Cox regression. <h3>Results</h3> Twenty-one SSc patients in the combination group were compared to sixteen in the AHSCT group. There were no significant differences in the demographic or clinical variables, except for Nintedanib treatment (<b>Table 1</b>). CI at 12 months was seen in 86% of patients in the combination group, compared to 81% in the AHSCT group (p=0.7). The hazard ratio (HR) for EFS at 24 months favored the combination group (HR=0.09, 95% CI 0.009 to 0.9; P =0.04). In both groups, a statistically significant and similar increase in FVC values, but not in DLCO, was demonstrated at each time point during follow-up. The inclusion of Nintedanib usage in the mixed model did not influence these results. In both groups, there was a significant and similar reduction in mRSS at 12 and 24 months compared to baseline (<b>Figure 1).</b> <h3>Conclusion</h3> In our cohort, combination therapy of MMF and rituximab compared to AHSCT in SSc patients eligible for AHSCT, resulted in similar skin and lung clinical improvement with a better safety profile after 24 months. <h3>References</h3> [1]Shouval R, Furie N, Raanani P, et al. Autologous Hematopoietic Stem Cell Transplantation for Systemic Sclerosis: A Systematic Review and Meta-Analysis. Biol Blood Marrow Transplant. 2018; 24:937-944. [2]Sullivan K, Tashkin, D, Pinckney, A et al. Progressive deterioration of patients with scleroderma with pulmonary involvement:11 years outcomes from the scleroderma lung study (SLS1). Clinical and experimental rheumatology. 32. S17-S18. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.